The construction of compact and monolithic chip-sized laboratories and reaction systems is now possible with the advent of dense integration of microfluidic components on small chips. Chip-sized laboratories and reaction systems can analyze and/or process very small samples of liquids, for example, samples in the 10-200 nano-Liter (nL) size range. Such chip-sized laboratories and reaction systems require many different functions to be miniaturized and combined on a common substrate. Some useful chip-based operations include mixing, filtering, metering, pumping, reacting, sensing, heating and cooling of nano-liter volumes of sample fluids. In such systems, smaller amounts of samples can be analyzed in less time, as little material is lost by transferring samples from one reaction vessel to another. So far, much work has been performed on defining and integrating fluidic components that can perform such on-chip mixing, sorting, and reacting of fluids. By combining thousands of lithographically defined pumps and valves into chip-based systems, it is possible to obtain unprecedented control over reagent concentrations and perform many reactions in parallel. However, one largely unexplored area for microfluidic devices has been the miniaturization of thermal management systems, such as refrigerators and heaters to control the local temperature of a reaction. Typically, in the prior art, the entire chip is heated or cooled, which seriously limits the kind of independent operations that can be performed on such chips.
Many different approaches have so far been explored for thermal control, including the construction of resistive heating elements within fluidic chambers, and immersing the entire chip into coolant. For example, polymerase chain reaction (PCR) systems for DNA amplification have been fabricated with volumes as small as 12 nano-Liters based on lithographically defined resistive tungsten heaters. See J. Liu, M. Enzelberger, and S. R. Quake, Electrophoresis, 23, 1531 (2002) and Lagally E T, Simpson P C, Mathies R A, Sensors and Actuators B-Chemical 63 (3): 138-146 May 15, 2000.
The prior art approaches have several problems:
First, while they may address the heating of small fluidic volumes, they do not address the cooling of those volumes. Having started a reaction, once the reaction has reached its end point, it can be very important to stop it, such as by cooling it.
Second, both the heating and cooling of small fluidic volumes need be done quickly.
Third, the small fluidic volumes need to remain captured while being heated. A common material currently used for microfluidic devices is polydimethylsiloxane (PDMS). PDMS is used since it enjoys good mechanical and thermal properties. However, one draw back of PDMS is that fluids, when heated, are likely to seep into the PDMS material. This is unsatisfactory for at least two reasons: (i) the samples under test are partially or totally lost when heated and (ii) the microfluidic device becomes contaminated by the seeping fluids.
This disclosure demonstrates that micro-Peltier junctions provide good mechanisms for heating and cooling of samples in microfluidic devices. And the patent application which is incorporated by reference explains in even greater detail than is explained below how certain special materials can be used to provide a very thin fluid-impervious layer on PDMS so that heating/cooling chambers provided in microfluidic devices made from PDMS can be protected against fluid samples seeping out of the heating/cooling chambers and into the surrounding PDMS material.
Furthermore, use of micro-Peltier junctions provides an even more versatile method of thermal control, which permits both local heating and cooling of reaction chambers and the controlled redistribution of heat loads on microfluidic chips. The integration of such heating and refrigeration systems with microfluidic valves and pumps is straight forward. The present disclosure describes the temperature dependence on the current applied to micro-Peltier junctions as well as the microfluidic heat exchange flow. The technology described here is expected to be particularly useful for the definition of micro-PCR systems, as well as for many analytical biochemical reaction and testing systems.